It has been repeatedly suggested that chromosomal translocations may be involved in the pathogenesis of certain tumors by altering the levels of expression of cellular oncogenes. Recent work by this researcher and others has indicated that the human c-myc oncogene is located on chromosome 8 (q24). This region is involved in specific translocations found in a subset of acute nonlymphoblastic leukemias, different types of undifferentiated B-cell lymphomas (UBL), and a familiar abnormality that predisposes to renal cell carcinoma. In some cases of UBL characterized by the t(8:14) translocation, the breakpoint on chromosome 8 appears to occur in the 5' flanking region of the c-myc gene, leading to its direct translocation into the immunoglobulin heavy chain locus (IHC) on chromosome 14. This event has been directly demonstrated by cloning the crossover region between chromosome 8 and 14 from the genome of a UBL cell line. On the basis of these findings, the following studies are underway: (1)\DNA from leukemias and lymphoma cells carrying chromosome 8 abnormalities (trisomy, t(8:14), t(8:2), t(8:22), t(8:21), deletions and rearrangements) will be examined by the Southern blotting technique using cloned human c-myc probes to determine whether c-myc rearrangements are detectable; (2)\in selected cases, c-myc expression will be studied at different levels, namely DNA methylation, chromatin structure, mRNA levels, and protein production; (3)\the genomic structure of a translocated and rearranged c-myc locus will be studied in DNA clones which contain the crossover points between chromosomes 8 and 14 in the t(8:14) translocation. These clones, obtained from Burkitt's lymphoma cells, will be studied by restriction enzyme analysis and DNA sequencing; and (4)\clones containing the rearranged c-myc gene will be assayed for their transforming potential in several DNA transfection systems including NIH 3T3, human fibroblasts, normal human lymphocytes, and human B lymphoblastoid cell lines. (X)